Butenylene bis



Patented Oct. 17, 1950 BUTENYLENE BIS (AMMONIUM HALIDES) Peter L. deBonneville, Philadelphia, Pa., assignor to Rohm & Haas Company,Philadelphia, Pa., a

corporation of Delaware No Drawing. Application June 29, 1949, SerialNo. 102,141

4 Claims. (Cl. 260-25675) This invention relates toN,N,N',N'-tetramethyl-N11bis-alkylbenzyl-N,N'-2-butenylenel,4-bis(ammonium halides) and to aprocess by which these bis quaternary ammonium halides are prepared.They are powerful bacteriostatic, bactericidal, and fungicidal agents.

These compounds are defined by the formula CH: CH: CH: CH:

wherein R is an alkyl group of seven to nine carbon atoms, R" ishydrogen or the methyl group, and X is a halogen, particularly bromineor chlorine, having an atomic weight between 35 and 80.

These compounds are prepared by reacting together in a molar ratio ofabout one to two 1,4-bis(dimethylamino) -2-butene and an alkylbenzylhalide in which the alkyl group has seven to nine carbon atoms. The tworeactants may be combined directly or they may be reacted by addition inthe presence of an inert organic solvent such as benzene, toluene,xylene, isopropyl alcohol, butyl alcohol, isopropyl ether, anitroparaflin such as nitromethane, acetonitrile, formamide, or thelike. Temperatures from 20 C. up to 140 C. may be used for the reaction.Solvents, when used, are generally removed by distillation at normal orreduced pressure and the bis quaternary salt is recovered as a residue.Some of the quaternary salts are precipitated or crystallized from thesolvents.

' Preparation of 1,4 bis(dimethylamino) 2- butene is described byWillstatter and Wirth, Ber. 46, 537 (1913), dibromobutene being reactedwith dimethylamine. Other methods of preparation will be evident tothose skilled in the art and may be used to yield this startingmaterial. Alkylbenzyl halides having alkyl groups of the required sizeare prepared in accordance with the method described in our applicationSerial No. 28,274, filed May 20, 1948. As there described, alkylbenzylhalides are obtained by halomethylating an alkylbcnzene or analkyltoluene by reaction with anhydrous formaldehyde and hydrogenchloride or bromide in the presence of a catalyst mixture formed fromone molecular proportion of zinc chloride and 1.5 to 8 molecularproportions of an aliphatic monocarboxylic acid of one to three carbonatoms, such as formic, acetic, chloracetic, or propionic. An acidanhydride may be used in place of these acids or in admixture therewith.Formaldehyde may be used as a gas or as a. revertible polymer. Theequivalent of formaldehyde and hydrogen bromide or hydrogen chloride isobtained by use of bromomethyl ether or chloromethyl ether, which areconveniently prepared by known methods and reacted with an alkylbenzeneof the required size.

For halomethylation of alkylbenzenes or alkyltoluenes having alkylgroups of seven to nine carbon atoms from one to 2.5 molecularequivalents of formaldehyde together with 0.75 to 2.5 molecularproportions of zinc chloride taken with 1.5 to 8 molecular proportionsof aliphatic monocarboxylic acid per mole of zinc chloride are used permole of an alkylbenzene or alkyltoluene. These components are mixed andstirred at temperatures of 50 to C. and hydrogen chloride or bromide ispassed in. Alternatively, the alkylbenzene and catalyst mixture arestirred together and a halomethyl ether added with observance of thedefined proportions. With a heptyl benzene it is advisable for bestyields to work at the lower end of the temperature range with an upperproportion of monocarboxylic acid within the designated range. Yieldsimprove with increasing size of alkyl group. By this procedure goodyields of alkylbenzyl halides are obtained with introduction almostentirely of a single halomethylgroup and without formation oftroublesome resinous products.

For preparation of the alkyl-benzyl halides there are requiredalkylbenzenes or alkyltoluenes of the proper tize. The exact form of thealkyl group is not important, nor is the orientation of this grouprelative to the halomethyl group or to the methyl group of analkyltoluene of particular significance. The alkyl group may be ofstraight or branched chain structure and may be primary, secondary ortertiary. This group may be introduced by known methods. For example, anacyl halide may be used to introduce an acyl group into the phenyl ring,which is then reduced. Oleflnic hydrocarbons of the required size may bereacted with benzene or toluene in the presence of an acidic catalyst.

The useful starting alkylbenzenes are heptylbenzene, octylbenzene,nonylbenzene, heptyltoluene, octyltoluene. and nonyltoluene in theirvarious isomeric forms. Typical of these are (1- methylhexyl) benzene,(l-ethylpentyl) -benzene, (1,B-dimethyl-l-propylbutyl) benzene,(l-methylheptyl) benzene, (Z-ethylhexyl) benzene, (3,5,5-trimethylhexyl) benzene, 0-, m-, or p-octyltoluene, p-(l-methylheptyl)toluene, p-(l-ethylpentyl) toluene, (1,3,3-trimethylbutyl)-benzene,

' arated into layers.

and the like. Mixtures of such hydrocarbons may be used as well asindividual alkylbenzenes or alkyltoluenes.

Typical preparations of alkylbenzyl halides follow. Parts shown are byweight.

Example 1.--To a mixture of 70 parts of 2-ethylhexylbenzene (preparedaccording to the method of Sulzbacher and Bergmann, J. Org. Chem. 13,303 (1948)), 50.3 parts of anhydrous zinc chloride, and. 60 parts ofglacial acetic acid there was added with stirring 42.5 parts ofdichloromethyl ether over the course of an hour, while the reactionmixture was maintained at 60 C. Stirring was continued for another twohours with the temperature held at 60 C. Layers were then allowed toform and separated. The product layer was washed with sodium bicarbonatesolution and distilled at 110125 C./0.07 mm. The distillate correspondedin composition to 2-ethylhexylbenzyl chloride.

Example 2.To a mixture of 138 parts by weight of toluene and 90 parts ofanhydrous hydrogen fluoride, contained in a copper flask and held at -10C., there was added 336 parts of mixed octenes, boiling at 123-134 C.,at such a rate that the temperature did not rise above 10 C. Thereaction mixture was stirred for an hour and then poured upon ice. Theorganic layer was separated, washed with water, with sodium bicarbonatesolution, and again with water, dried over calcium chloride, and finallydistilled. Unreacted toluene and octene were removed and the organicliquid stripped by heatin to 115 (LL/35 mm. There was then obtained afraction between 135 C./35 mm. and 155 C./0.5 mm. which consistedessentially of octyltoluenes.

A mixture was made in the reaction vessel equipped with a, stirrer of 32parts of octyltoluene, 25 parts of anhydrous zinc chloride, and 60 partsof glacial acetic acid. With the temperature kept at 50 to 60 C. therewas added thereto 20 parts of dichloromethyl ether. The temperature ofthe mixture was then raised to 90 C. for three hours. The reactionmixture was then sep- The product layer was washed with water, with a 5%sodium bicarbonate solution, and again with water. Upon distillation afraction was obtained at 133-148 C./0.3 mm. which corresponded incomposition to 2-methyl-5-octylbenzyl chloride.

Example 3.Commercial diisobutyl carbinol was dripped slowly over a, bedof alumina at 400 C. The vapors were taken oil and condensed. Therefromnonene was separated and distilled at 72-75 C./100 mm. The product,containing by analysis 85.7% of carbon and 14.3% of hydrogen, was2,6-dimethyl-3-heptene, for which the theoretical content of carbon is85.8% and of hydrogen is 14.3%.

There was added 135 parts by weight of this product to a stirred mixtureof 159 parts of benzene and 147 parts of sulfuric acid. The temperaturewas held between 0 and C. After the mixture had been stirred for threehours, it was allowed to form layers. The upper layer was distilled andthe distillate redistilled at 102-106 C./3 mm. This distillate had amolecular weight of 203 (theory 204) and corresponded in composition tononylbenzene. The yield was 95 parts.

To a mixture of 80 parts of nonylbenzene, 40 parts of zinc chloride, and59 parts of glacial acetic acid there was added at room temperature 45parts of dichloromethyl ether. The mixture was stirred and heated at 70C. for three hours. It was then allowed to stand and form layers. Theupper layer was separated, washed with hot water, and with sodiumbicarbonate solution, dried over sodium sulfate, and distilled. Thefraction distilling at 141-142 C./2 mm. was nonylbenzyl chloride.

Example 4.-T0 a mixture of 184 parts of toluene and 103 parts ofsulfuric acid there was added 112 parts of octene while the mixture wasstirred and held at 5-13 C. The octene had been prepared by dehydrationof capryl alcohol on an alumina catalyst (of. Komarewsky, Ulick, andMurray, J. Am. Chem. Soc. 67, 557 (1945)). The reaction mixture wasstirred for three hours at room temperature, and the product layer wasseparated. It was washed twice with concentrated sulfuric acid anddistilled. The fraction taken at 93-95 C./ 0.3 mm. corresponded incomposition to sec.-octylmethylbenzene.

To a mixture of 81 parts of this product, 47.5 parts of anhydrous zincchloride, and 65 parts of glacial acetic acid there was added 46 partsof diand held at 50-60 C. for an hour. It was stirred at 70-75 C. forfour hours and allowed to form layers. The upper layer was separated,washed with water and sodium bicarbonate solution, and distilled. Thefraction taken at 130-150 C./0.3 mm. amounted to 43.8 parts andcorresponded in composition to methyloctylbenzyl chloride.

Example 5.-Commercia1 3-heptanol was dehydrated on an alumina catalystat 400 C. to yield a mixture of 2-heptene and 3-heptene which wascondensed and distilled.

There were mixed 125 parts of this product, 198 parts of benzene, and196 parts of concentrated sulfuric acid while the mixture was stirredand held at 5 C. The mixture was stirred for three hours with thetemperature of the mixture being allowed to advance above roomtemperature. Layers were permitted to form and the upper layer wastaken. It was twice washed with sulfuric acid and distilled to yield 167parts of heptylbenzene, probably a mixture of 2-heptylbenzene and3-heptylbenzene. The product had a carbon content of 87.3% and ahydrogen content of 11.7%, compared with theoretical values of 88.6% and11.7% respectively.

There were mixed 160 parts of this product, 99 parts of anhydrous zincchloride, and 138 parts of glacial acetic acid. Thereto was added at 60C. 106 parts of dichloromethyl ether. The mixture was stirred for fourhours and then allowed to stand and separate into layers. The upperlayer was washed with water, with sodium bicarbonate solution, and withwater and then distilled. At 127-132 C./2 mm. there was obtained afraction of 128 parts which corresponded in composition to heptylbenzylchloride.

Example 6.A mixture of parts by weight of octylbenzene (chiefly2-octylbenzene with some 3-octylbenzene), 30 parts of paraformaldehyde,54 parts of anhydrous zinc chloride, and parts of glacial acetic acidwas stirred at 50C. while hydrogen chloride was passed in for two hoursat a fairly rapid rate. The reaction mixture was allowed to stratify andthe upper layer was taken, washed with hot water, with a 10% sodiumbicarbonate solution, and with hot water, dried over sodium sulfate anddistilled. The forerun of 30 parts consisted of octylbenzene. There wasthen obtained at 119-l21 C./1 mm. 71 parts of octylbenzyl chloride.

Example 7 .--To a mixture of 46.5 parts of octylbenzene (chiefly2-octylbensene) 1'! parts at anhydrous zinc chloride. and 40 parts ofglacial acetic acid there was added dropwise 50 parts of bis-bromomethylether. The mixture was stirred and heated at 70' C. for four hours inall. Layers were allowed to form and were separated. The upper layer waswashed with hot water, with sodium bicarbonate solution, and with water.It was dried over sodium sulfate and distilled.

At 155-174 c./2 mm. there was obtained a iraction corresponding incomposition to octylbenzyl bromide. It contained by analysis 28.8% 01'bromine. Theory for this product is 28.3%.

In the following examples the reaction 01 aikylbenzyl halidesand1,4-bis(dimethylamim) -2 -bl1- tene is illustrated.

Example 8.-There were mixed 135 parts of heptylbenzyl chloride and 42.6parts of 1,4-bis(dimethylaminol-2-butene in 250 parts of benzene. Themixture was heated at reflux temperature for three hours. The benzenewas then removed by distillation and stripped of! by heating on a, steambath under low pressure. There was obtained a residue amounting to 180parts which on analysis was found to contain 11.4% of chlorine. Thecompound obtained was N.N,N',N,-tetramethyl- N,N'-bis(heptylbenzyl)N,N'-2-butenylene-1,4- bis(ammonium chloride).

This compound has a phenol coetllcient of 300 against Salmonella tpphosaand of 1000 against Staphylococcus aureus. It eflectively inhibitsgermination of spores of Sclerotlnia ,frueticola and Macrosporiumsarcinneforme at dilutions of 0.001% to 0.005%.

The method shown above when applied to the reaction of hexylbenzylchloride and bis(dimethylamlno) -2-butene leads to the comparabletetramethyl bis-hexylbenzyl butenylene bis(ammonium chloride). Thiscompound has far less bactericidal activity than the above heptylbenzylcompound, the phenol coeflicient therefor being below 100.

Example V9.-There were mixed '71 parts by weight orbis(dimethylamino)-2-butene and 238 parts of p-(l-methylheptyl) benzylchloride in 600 parts of benzene. The mixture was heated at refluxtemperature for four hours. The solvent was then removed by distillationwith stripping at reduced pressure. The product was obtained as aresidue. It corresponded in composition to N,N,N',N'- tetramethyl-N.N'-p-l-methylheptylbenzyl-2- butenylene -1.4- bis(ammonium chloride).

The phenol coemcient of this product is 775 against Salmonella typhosaand 855 against Staphylococcus aureus.

Example 10.-There were mixed 35.5 parts of bis(dimethylamino) -2-buteneand 142 parts of p-2-octylbenzy1 bromide in 250 parts of benzene. Themixture was stirred and heated with vigorous reflux for 2.5 hours. Thesolvent was removed by distillation andN,N,N',N'-tetramethyl-N,N'-poctylbenzy1-2-butenylene-l,4-bis(ammoniumbromide) obtained as a residue. It has a phenol coefllcient oi 950against Staphylococcus aureus and 800 against Salmonella iWhOIl-l. It isan efiective fungicide.

Example 11.-There were mixed 125 parts of p-(1-isopropyl-4-methylpentyl)-benzyl chloride. 35 parts of 1,4-bis(dimethylamino) -2-butene, and 250parts of toluene. The mixture was heated at reflux tem erature for twohours. The product p was obtained in the form or light pink crystals,

which were separated and dried. They contained 6 10.98%). This productwas N.N.N',N"-tetramethyl- N.N'-bis (p-1-isopropyl-4-methylpentylbenzyl)-2- butenylene-1,4-bis(ammonium chloride). It has phenol coeflicients or555 against Salmonella typhosa and of 500 against Staphylococcus aureus.

It is of interest that when the comparable salt was made from adecylbenzyl chloride and bis(dimethylamino) -2-butene by the sameprocedure the product had a phenol coeflicient of 42 againstStaphylococcus aureus.

Example 12.There were mixed 35 parts of bis(dimethylamino) -2-butene,125 parts of 2- methyl-5-sec.-octylbenzy1 chloride, and 300 parts ofbenzene. The mixture was heated under reflux ior five hours. The benzenewas distilled ofi under reduced pressure. The product obtainedcorresponds in composition to N,N,N',N'-tetramethyl -N,N-bis(2-methyl-5- sec.-octylbenzyl)- 2-butenylene-L4-bis(ammoniumchloride). It has a phenol coeilicient of 800 against Salmonella typhosaand of 850 against Staphylococcus aureus.

The group of his quaternary ammonium chlorides and bromides here claimedcomprises peculiarly effective bactericides and fungicides. The highdegree of effectiveness rests in large part upon the size of the alkylsubstituent of the benzyl groups, as is evident from the data. Thehalides as prepared above may be converted to other quatenary salts byinterchange of another anion for the halide, such as pentachlorophenate,nitrophenate, acetate, sulfate, and the like.

By an alternative method for the preparation of theN,N,N',N-tetramethyl-N,N'-bis(alkylbenzyl) -N,N'-2- butenylene -1,4-bis(ammonium halides) there are reacted two moles of analkylbenzyldimethylamine and one mole of 1,4-dibromo-Z-butene orlA-dichloro-z-butene. As above the alkyl group must contain seven tonine carbon atoms. The conditions for eflecting this reaction areessentially the same as for the reaction of 1,4-bis(dimethylamino)-2-butene and an alkylbenzyl halide.

Typical preparations of alkylbenzyldimethylamines follow:

Example 13.(a) To a solution or 8 parts of sodium hydroxide in 30 partsof water there was added 22.5 parts of an aqueous 40% dimthylaminesolution. The reaction vessel in which this mixture was formed carried arefluxing system cooled with dry ice and acetone. To the mixture therewas added 22.5 parts of heptylbenzyl chloride. The mixture was heated togive gentle refluxing and dimethylamine gas was slowly passed in duringa period of three hours. The reaction mixture was allowed to form layerswhich were separated. The product layer was washed with water untilneutral to litmus and heated under reduced pressure. There was obtained20 parts of a, light yellow oil which had the proper analysis forheptylbenzyldimethylamine.

(b) The procedure of Example 13 (a) was followed with substitution of25.3 parts of nonylbenzyl chloride in place of the 22.5 parts ofheptylbenzyl chloride. There was obtained 18 parts of product whichcorresponded by nitrogen analysis to nonylbenzyldimethylamine.

The procedure was repeated with p-1,3,5, tetramethylpentylbenzylchloride and a similar product obtained, p-(1.3.5.5-tetramethylpentyl)benzyldimethylamine,

(c) The procedure of Example 13 (a) was followed with use of 23.8 partsof p-2-octylbenzyl by analysis 10.72% of ionizable chlorinehtheorychloride as the alkylbenzyl halide. The product 7 obtained was (2octylbenzyl) dimethylamine.

An alkylbenzyldimethylamine and a dihalobutene are reacted at 20 to 140C. with or without an organic solvent. Typical of this reaction are thefollowing examples.

Example 14.There were mixed 63 parts of p- (l-methylheptyl)benzyldimethylamine, 43 parts of 1,4-dibromo-2-butene, and 125 parts ofbenzene. The mixture was heated under reflux for sixteen hours and thesolvent stripped 011. There was obtained a residue which corresponded incomposition to N,N,N,N' tetramethy1-N,N'-bis-p- (1- methylheptyl) benzyl2 butenylene-l,4-bls(ammonium bromide). This product has a phenolcoeflicient of 970 against Staphylococcus aureus and of 810 againstSalmonella typhosa.

I claim:

1. As new chemical substances, compounds of the formula:

a on; CH; CH; cm

RI! II wherein R is an alkyl group of seven to nine carbon atoms, R" isa member of the class consisting of hydrogen and the methyl group, and Xis a member of the class consisting of chlorine and bromine.

2. As a new chemical substance, N,N,N',N'-tetramethyl-N,N-bis(nonylbenzyl) 2 butenylene-1,4-bis(ammonium chloride)3. As a new chemical substance, N,N,N',N'- tetramethy1-N,N'-bis(octylbenzyl) 2 butenylene-1,4-bis(ammonium chloride) 4. As a new chemicalsubstance, N,N,N',N'- tetramethyl-N,N'-bis(octyl benzyl) 2butenylene-l,4-bis(ammonium bromide).

PETER L. on BENNEVILLE.

No references cited.

1. AS NEW CHEMICAL SUBSTANCES, COMPOUNDS OF THE FORMULA: